DESIGN, SYNTHESIS, MOLECULAR DOCKING AND ANTI-BREAST CANCER ACTIVITY OF NOVEL QUINAZOLINONES TARGETING ESTROGEN RECEPTOR α

A new series of 6.8-dibromo-2-(4-chlorophenyl)-4-oxo-4H-quinazoline derivatives II-VI were synthesized, their chemical structures were confirmed by spectroscopic means and elemental analyses. All these compounds were tested in rim, against human breast cancer cell line (MCF-7) using resazurin reduction assay method and doxorubicin as a reference drug. Most of the tested compounds showed better activity than doxorubicin. Compound IVh was the best active one, its IC50, is 8.52 mu g/mL. Molecular docking studies for the best active compounds IVb. IVc, IVf, IVh and Vu were performed on the active site of estrogen receptor a (ER alpha) subtype to explore the estrogen receptor binding ability of these compounds. All the docked compounds showed good fitting score energy with the active site of ERa subtype and compound IVh showed the best docking score energy( -25.3 kcal/mol). Estrogen binding evaluation assay was performed for the docked compounds to ensure that their activity against MCF7 go through inhibition of ERa, they showed ERa inhibition at 41-85% and compound IVh was the roost active one (85%).